Harenberg J, Schneider D, Heilmann L, Wolf H
1st Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Klinikum Mannheim, FRG.
Haemostasis. 1993 Nov-Dec;23(6):314-20. doi: 10.1159/000216894.
Prophylaxis of thromboembolism with low molecular mass (LMM) heparin may offer several advantages over conventional heparin during pregnancy. Heparin-related side effects as osteoporosis, local allergy, thrombocytopenia and increase in liver enzymes may occur less frequently with LMM heparin. However, LMM heparins of different origins have to be considered as individual pharmaceutical compounds. This is of special clinical importance regarding a possible placental passage. We performed a randomized controlled study comparing the anti-factor Xa activities in plasma samples of 60 pregnant women undergoing delivery at term and in the umbilical cord vein of the newborn after subcutaneous administration of 5,000 IU unfractionated (UF) heparin or 1,500 activated partial thromboplastin time units LMM heparin or placebo. Injections were performed about 2 h prior to the delivery. Maternal and fetal blood samples were taken at the same time to assay heparin activity by the heptest coagulation assay and the S2222 chromogenic substrate method. LMM heparin was detected in all maternal plasma samples whereas UF heparin was measurable only in about one third of them. UF heparin as well as LMM heparin were not detectable in samples taken from the umbilical cord vein. The data demonstrate that neither UF nor the LMM heparin used in this study cross the placenta in relevant inhibitory activity towards factor Xa. This finding is in accordance with the previous experiences regarding the safe administration of other LMM heparins for prophylaxis of thromboembolism during pregnancy.
在孕期,与传统肝素相比,使用低分子量(LMM)肝素预防血栓栓塞可能具有若干优势。LMM肝素引发的与肝素相关的副作用,如骨质疏松、局部过敏、血小板减少和肝酶升高,可能较少发生。然而,不同来源的LMM肝素必须被视为独立的药物化合物。这对于可能的胎盘转运具有特殊的临床重要性。我们进行了一项随机对照研究,比较了60名足月分娩孕妇皮下注射5000 IU普通肝素(UF)、1500活化部分凝血活酶时间单位LMM肝素或安慰剂后,母体血浆样本和新生儿脐静脉中抗Xa因子活性。在分娩前约2小时进行注射。同时采集母体和胎儿血液样本,通过七因子凝血试验和S2222显色底物法测定肝素活性。在所有母体血浆样本中均检测到LMM肝素,而UF肝素仅在约三分之一的样本中可检测到。从脐静脉采集的样本中未检测到UF肝素和LMM肝素。数据表明,本研究中使用的UF肝素和LMM肝素均未以对Xa因子的相关抑制活性穿过胎盘。这一发现与先前关于在孕期安全使用其他LMM肝素预防血栓栓塞的经验一致。